The present invention relates to the technical field of immunology and the treatment of diseases mediated and/or indicated by the presence of a ligand of NK receptor NKG2D, such as major histocompatibility complex class I chain related (MIC) A and B molecules on the cell surface of diseased tissue or cells. In particular, the present invention makes use of the surprising finding that the stress-inducible endogenous danger signals HSP70 and MICA/B synergistically activate NK cells against tumors. Methods and compositions for the prevention and treatment of infectious diseases, primary and in particular metastatic neoplastic diseases, including, but not limited to human sarcomas, carcinomas and melanomas are provided.